The present invention relates to a method for the topical treatment of fungal diseases in nails. This invention relates in particular to a composition for enhancing the permeation rate of antifungal agents in nails and to an apparatus adapted for use with the testing of the invention.
All living things can be classified into one of five fundamental kingdoms of life and the term fungus refers generically to all members of the Kingdom Fungi. There are more than a million species of fungi but only about 400 cause diseases relevant to man.
Infections of the nail are so important that they get their own name. The term onychomycosis is used both to refer to non-dermatophyte nail infections and to any fungal nail infection caused by any fungus. The term tinea unguium can be applied only if the infection is due to a dermatophyte. The distinction is narrow and technical. The leading yeast cause of onychomycosis is candida albicans. It is not uncommon to have more than one fungus species jointly causing the infection.
The dermatophytes are not a particular fungus but rather a common short-hand label for a group of three genera of fungi that commonly cause skin disease of people:                (a) Epidermophyton floccosum is a common cause of dermatophytosis in otherwise healthy individuals. It infects skin and nails. The infection is restricted to the nonliving cornified layers of epidermis since the fungus lacks the ability to penetrate the viable tissues of the immunocompetent host (Aman, S., T. S. Haroon, I. Hussain, M. A. Bokhari, and K. Khurshid. 2001. Tinea unguium in Lahore, Pakistan. Med Mycol. 39:177-180). Disseminated infections due to any of the dermatophytes are very unlikely due to the restriction of the infection to keratinized tissues. Epidermophyton floccosum infections are communicable and usually transmitted by contact.        (b) Trichophyton is a causative agent of dermatophytosis and infects the skin and nails (Aly, R., R. J. Hay, A. Del Palacio, and R. Galimberti. 2000. Epidemiology of tinea capitis. Med Mycol. 38:183-188). Trichophyton is a keratinophilic filamentous fungus. Ability to invade keratinized tissues and the possession of several enzymes are the major virulence factors of these fungi (Weitzman, I., and R. C. Summerbell. 1995. The dermatophytes. Clin Microbiol Rev. 8:240-59).        (c) Microsporum is a genus that causes dermatophytosis. Dermatophytosis is a general term used to define the infection in skin or nails due to any dermatophyte species. Microsporum has the ability to degrade keratin and thus can reside on skin and its appendages and remains noninvasive. Proteinases and elastases of the fungus may act as virulence factors. Microsporum spp. mostly infects the skin. Nail infections are very rare. The pathogenesis of the infection depends on the natural reservoir of the species. Geophilic spp. is acquired via contact with soil. Zoophilic species are transmitted from the infected animal. Direct or indirect human-to-human transmission is of concern for anthropophilic species. Asymptomatic carriage may be observed. Otherwise healthy hosts are infected (Aly, R. 1999. Ecology, epidemiology and diagnosis of tinea capitis. Pediat Inf. Dis J. 18:180-185).        
Candida is thin-walled yeast that reproduces by budding. No more than ten species of Candida cause disease in humans with any frequency even though there are more than 150 species (Kwon-Chung, K. J., and J. E. Bennett. 1992. Medical Mycology. Lea & Febiger, Philadelphia).
Cutaneous candidiasis is arguably the most common form of candidiasis. The infection involves the very outer-most layers of the skin. Healthy skin is quite resistant to candidal infection and in essentially all cases a predisposing factor is present. These forms of localized candiasis can be very irritating to the patient although neither invasive nor life-threatening. The most common and important form of candidal skin infections is erosio interdigitalis blastomycetica in the finger or toe webspace with eroded erythematous area surrounded with macerated skin.